Purpose:To evaluate the effectiveness of corneal cross-linking in improving the signs and symptoms of bullous keratopathy.Materials and Methods:This prospective non-randomized case series evaluated 20 eyes with bullous ketratopathy that underwent corneal cross-linking (C3R) with riboflavin and ultraviolet-A (UVA, 370 nm, 3 mW/cm2). C3R was performed for 30 min in a routine procedure after removal of epithelium. Central corneal thickness (CCT), corneal haze, visual acuity (VA), and the presence of irritating symptoms were recorded before the procedure, and at 1 week, 1 months, 3 months, and 6 months after the procedure.Results:The mean CCT was 872 ± 162 μm (range: 665-1180 μm) before the procedure. Following the procedure, CCT was 855 ± 175 μm after 1 week, 839 ± 210 μm after 1 month, 866 ± 185 μm after 3 months, and 863 ± 177 μm after 6 months (P>0.05, all visits). There was no significant improvement in VA or corneal clarity after 6 months. Improvement of the following symptoms: burning, pain, and foreign body sensation were reported after 6 months by 83.3%, 75.0%, and 66.7% of patients, respectively. Persistent epithelial defect occurred in five patients (25%) resolved with frequent lubrication and bandage contact lenses.Conclusion:The outcomes of this study indicate corneal cross-linking is not an effective treatment for bullous keratopathy with respect to VA and CCT, although it can improve irritation and discomfort.